ABSTRACT The primary goal of this timely and significant services planning grant is to understand the facilitating factors and barriers in Appalachia associated with the continuum of care at re-entry for persons who inject opioids (PWIOs) who do and do not initiate extended-release injectable naltrexone (XR-NTX, Vivitrol, Alkermes Inc.) while in prison. An ecological theoretical framework will be used to understand individual characteristics that predict treatment successes, as well as contexts more distal to the individual, including social networks and institutional factors in the healthcare and justice systems. A mixed methods approach will be used to carry out this natural history study. Building upon an existing dataset of intake assessments for all inmates participating in treatment in KY prisons, this study will collect follow-up survey and personal network data 3-months post-release from 150 PWIOs who are returning to Appalachian counties. Qualitative data collection includes open-ended questions in the follow-up interview for PWIOs who initiated XR-NTX in prison and in-depth interviews with 13 social service clinicians. Specific aims include: (1) To identify the individual- level factors, including XR-NTX initiation, and personal (egocentric) network factors associated with continuity of care and adverse health outcomes among re-entering Appalachian PWIOs, and (2) To describe individual, network, and institutional gaps in the XR-NTX continuum of care among Appalachian PWIOs re-entering the community after initiating XR-NTX in prison. This study is highly significant due to the opioid injection epidemic, high overdose rates in Appalachian Kentucky, and limited available information on treatment outcomes during the vulnerable re-entry period when XR-NTX is implemented by a prison under natural conditions. Innovation is high based on the lack of social network studies in Appalachian or justice-involved populations, the focus on networks? social influence during the high-risk time after release, and the Kentucky legislative policy changes allowing prison-based XR-NTX initiation to improve offender post-release outcomes. Findings will inform future process improvement efforts for the XR-NTX continuum of care in resource-limited Appalachian counties, apply network science findings to improve the re-entry planning process, and inform future R-level applications.